UPMC Physician Resources

Race and Ethnicity Important When Evaluating Risk of Fat Around the Heart

PITTSBURGH, Sept. 9, 2014 – A man’s likelihood of accumulating fat around his heart – an important indicator of heart disease risk – may be better determined if doctors consider his race and ethnicity, as well as where on his body he’s building up excess fat, reveals an international evaluation led by the University of Pittsburgh Graduate School of Public Health

The findings, published online today in the International Journal of Obesity, indicate that it may be useful to take racial and ethnic differences into account when designing programs to reduce obesity because what works for one man might not be as beneficial for another.  This analysis was funded in part by the National Institutes of Health (NIH).

“If you are an African American man and carry excess weight mainly around the mid-section, then you have a higher likelihood of more fat around the heart than if you gain weight fairly evenly throughout your body,” said lead author Samar R. El Khoudary, Ph.D., M.P.H., assistant professor in Pitt Public Health’s Department of Epidemiology. “But the reverse is true for Koreans – their heart disease risk is greater with overall weight gain. Knowing this can help doctors specify the right physical training for each racial ethnic group to reduce their heart disease risk.”

Dr. El Khoudary’s analysis relied on data from the “Electron-Beam Tomography, Risk Factor Assessment Among Japanese and U.S. Men in the Post-World War II Birth Cohort Study,” also known as the ERA JUMP study. It is a population-based study of men enrolled between 2002 and 2006 who were ages 40 to 49 and free of cardiovascular disease, type-1 diabetes and other severe diseases at the time of enrollment.

The recent analysis took a closer look at 1,199 men in the study who were white or black from Allegheny County, Japanese-American from Hawaii, Japanese or Korean.

The study looked at the amount of fat around the heart called ectopic cardiovascular fat. Higher volumes of this fat are associated with greater risk of heart disease.

For white men, an increase in body mass index, or BMI, which is a measure of overall body fat, and abdominal fat are equally likely to indicate an increase in fat around the heart.

Compared to white men:

  • Black men who carry disproportionally more weight around their mid-section are at similar risk of having more fat around their hearts. Increases in BMI have lower impact.
  • Japanese and Japanese American men are also at similar risk of having more fat around their hearts if they have more fat in their abdomens, with BMI having less of an impact.
  • Korean men with higher BMIs have a higher likelihood of fat around the heart, whereas abdominal fat matters less.

“What we now need to determine is whether concentrating efforts to reduce overall body fat or fat in the abdomen will actually decrease fat around the heart more in people of certain racial or ethnic groups,” said Dr. El Khoudary. “Such a long-term evaluation could help in designing race-specific heart disease prevention strategies.”

The senior author and principal investigator on this study is Akira Sekikawa, M.D., Ph.D., Pitt. Additional authors on this study are Emma Berinas-Mitchell, Ph.D., Aiman El-Saed, M.D., Ph.D., Rhobert W. Evans, Ph.D., and Lewis H. Kuller, M.D., Dr.P.H., all of Pitt; Chol Shin, M.D., Ph.D., of Korea University; Kamal Masaki, M.D., and Bradley J. Willcox, M.D., both of the University of Hawaii; Katsuyuki Miura, M.D., Ph.D., Sakaya Kadowaki, M.D., Ph.D., Akira Fujiyoshi, M.D., M.P.H., Ph.D., Takashi Hisamatsu, M.D., Ph.D., and Hirotsugu Ueshima, M.D., Ph.D., all of Shiga University of Medical Science in Japan; Matthew Budoff, M.D., of Los Angeles Biomedical Research Institute; Daniel Edmundowicz, M.D., of Temple University School of Medicine; and Takayoshi Ohkubo, M.D., Ph.D., of Teikyo University School of Medicine in Japan.

This work was supported by NIH grants HL068200 and HL071561, Korea Center for Disease Control and Prevention government budget codes 2004-E71001-00 and 205-E71001-00, Japanese Ministry of Education, Culture Sports, Science and Technology grants B 16790335, A 13307016, 17209023, 21249043, A 25253046 and B 23390174.

2014 Marshall S. Levy, MD, Memorial Lecture

UPMC and the University of Pittsburgh Division of Rheumatology and Clinical Immunology are pleased to host Iain McInnes, PhD, as the guest lecturer for the 2014 Marshall S. Levy, MD, Memorial Lecture.

Professor McInnes currently serves as the Muirhead Chair of Medicine and Director of Institute of Infection, Immunity and Inflammation at the University of Glasgow.

He has a major interest in the biology of inflammatory synovitis in rheumatoid arthritis, psoriatic arthritis, and septic arthritis. He operates a translational science program in which state of the art cellular and molecular biology techniques are applied to elucidate the mechanisms underlying the perpetuation of synovial inflammation. In parallel they have an extensive clinical trials facility in which they perform studies of novel biologic agents in inflammatory arthritis.

Dr. McInnes has an established leadership role in translational medicine reflected in academic participation in the United Kingdom as the chair of the newly created Arthritis Research UK New Agents Committee, as the vice chair of the Medical Research Council Panel for Training and Fellowships, and the UK Clinical Research Network Specialty Groups Scottish Lead for Inflammation Medicine.

He has also served as chief or principal investigator at the global and national level for numerous phase I, II, and III drug development programs. As such he provides knowledge and experience in the conduct and translation of a variety of investigative modalities in the field of inflammation medicine.

Dr. McInnes’ lecture, Micro Molecules with Macro Effects in Rheumatology, will be presented on Friday, October 10, 2014.

Marshall S. Levy, MD, was a nephrologist at UPMC for nearly 40 years. During this time he served as the president of UPMC St. Margaret Hospital staff. He used his position to advocate for patients’ rights and concerns.

For more information on the lecture contact Hilary Peterson at HJP4@pitt.edu or 412-383-8100.

Unusual Immune Cell Needed to Prevent Oral Thrush, Pitt Researchers Find

PITTSBURGH, Sept. 8 – An unusual kind of immune cell in the tongue appears to play a pivotal role in the prevention of thrush, according to the researchers at the University of Pittsburgh School of Medicine who discovered them. The findings, published online today in the Journal of Experimental Medicine, might shed light on why people infected with HIV or who have other immune system impairments  are more susceptible to the oral yeast infection. 

Oral thrush is caused by an overgrowth of a normally present fungus called Candida albicans, which leads to painful white lesions in the mouth, said senior investigator Sarah L. Gaffen, Ph.D., professor, Division of Rheumatology and Clinical Immunology, Pitt School of Medicine. The infection is treatable, but is a common complication for people with HIV, transplant recipients who take drugs to suppress the immune system, chemotherapy patients and babies with immature immune systems. 

“In previous work, we found the cytokine interleukin-17 (IL-17), a protein involved in immune regulation, must be present to prevent the development of thrush,” Dr. Gaffen said. “But until now, we didn’t know where the IL-17 was coming from.” 

Typically, IL-17 is produced by immune T-cells that learn to recognize and remove a foreign organism after an initial exposure, known as adaptive immunity. But unlike humans, mice do not normally acquire Candida during birth and are considered immunologically naïve to it. When the researchers exposed the lab animals to Candida, their IL-17 levels rose within 24 hours despite the lack of a T-cell response. This suggested the immune activity was innate, rather than acquired. 

To find the cell responsible for IL-17 secretion, lead investigator Heather R. Conti, Ph.D., devised a way of applying a scientific technique called flow cytometry to sort for the first time cells gathered from the oral tissues. In the tongue, she identified unusual ones known as natural TH17 cells that looked very much like T-cells but didn’t behave like them. Subsequent tests showed that the novel cells did, indeed, make IL-17 when exposed to Candida. 

“These cells are part of a natural host defense system that is present at birth and does not require a first exposure to be activated,” Dr. Gaffen explained. “This study demonstrates for the first time that natural TH17 cells protect against infection.” 

The researchers speculate that the similarities natural TH17 cells share with T-cells make them vulnerable to HIV, chemotherapy and other agents as well, which could explain why certain people are more susceptible to oral thrush. Also, new drugs that block IL-17 soon will be on the market for treatment of rheumatologic conditions, so it’s possible that thrush could be a side effect. 

The team plans to examine the factors that influence thrush development within the high-risk groups.

 Co-authors of the paper include other researchers from the University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh of UPMC, the University of Pennsylvania, Genentech Inc., and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). 

The project was funded by NIH grants DE022550, AI107825, DE023815, AI095466, AI097333, AI106697, AI1110822, DE023293, AI098243 and T32-DK063922; Children’s Hospital of Pittsburgh of UPMC; the Pediatric Infectious Disease Society; the Edmond J. Safra Foundation/Cancer Research Institute; and the NIAID.

Children’s Brain Care Institute Experts Publish Paper that Supports Newborn Screening for Hurler Syndrome

PITTSBURGH, August 28, 2014 — Members of the Program for the Study of Neurodevelopment in Rare Disorders (NDRD) at Children’s Hospital of Pittsburgh of UPMC will have an article published in an upcoming issue of Annals of Neurology. The article, “Early Treatment is Associated With Improved Cognition in Hurler Syndrome,” was authored by Michele Poe, PhD, Sarah Chagnon, MD, and Maria Escolar, MD, of the Brain Care Institute.

Hurler syndrome is the most clinically severe form of an autosomal recessive lysosomal disorder characterized by the deficiency of α-L-iduronidase and is often fatal during childhood. Umbilical cord blood transplantation from unrelated donors has been shown to improve neurological outcomes of children younger than 2 years old, and extend the lives of these patients.

The authors followed 31 patients with Hurler syndrome who underwent umbilical cord blood transplantation between June 1997 and February 2013. Patients were evaluated at baseline and every six to 12 months thereafter. All 31 patients underwent complete neurodevelopmental evaluation and a median of seven evaluations. The authors found that younger age at transplantation was associated with improved cognitive function, receptive and expressive language, and adaptive behavior. Children younger than 9 months at the time of transplant showed normal cognitive development. These findings demonstrate that early diagnosis may be necessary for optimal outcomes and — because most patients are not identified at a young age — support the need for newborn screening.

Xiangya Hospital Partners with UPMC to Create World-Class Medical Center in China

PITTSBURGH, Aug. 25, 2014 Xiangya Hospital, Central South University, located in the Hunan Province of China, is partnering with UPMC to establish an international medical center that will improve access to high-quality care for patients within the region. Through this visionary relationship, Xiangya and UPMC expect to engage in a long-term collaboration.

As part of a five-year advisory services agreement with the 3,500-bed Chinese hospital, UPMC will help it to establish the Xiangya International Medical Center on the existing Changsha campus. The facility will offer world-class care to private-pay patients under a government-endorsed effort to relieve overcrowding in public hospitals by cooperating with private facilities. UPMC will serve as the exclusive advisor on the management of the International Medical Center and will participate in both medical and administrative oversight of all services.

“As one of the most respected medical centers in China, Xiangya Hospital is well positioned to expand its services and its reach throughout Asia. By partnering with one of the largest academic health care systems in the U.S. — and one that brings a wealth of international experience — we believe that the new Xiangya International Medical Center will quickly become a leader in providing the highest-quality medical care available in China,” said Sun Hong, M.D., Ph.D., president of Xiangya Hospital.

UPMC’s services will include training for medical and administrative staff both in China and in Pittsburgh, sharing of enhanced quality assurance and safety processes, recommendations on technology, equipment and staffing plans, and telemedicine links to UPMC’s clinical programs in Pittsburgh and Italy. A small number of UPMC staff also will be located at the hospital for consultative work.

“This clinical collaboration in China is UPMC’s most extensive effort yet in that country,” said Charles Bogosta, president of UPMC’s International and Commercial Services Division. “This effort will ensure that more patients receive the most advanced medical care close to home. At the same time, the financial and intellectual capital generated by this partnership will allow UPMC to advance its clinical and research missions in western Pennsylvania and beyond.”

UPMC’s informal relationship with Xiangya dates back nearly a decade, with physicians from both institutions and the University of Pittsburgh collaborating on patient care and research. “Xiangya has a long history of innovation in medical care and a reputation for advanced clinical programs, including organ transplantation,” noted Bruno Gridelli, M.D., medical and scientific director of UPMC’s International and Commercial Services Division. “We are excited about the potential to exchange knowledge and expertise with one of China’s best hospitals and to lay the groundwork for even greater collaboration in the future. Together, we are building a model for expanding access and raising the quality of health care throughout China.”

Established in 1906, the Xiangya Hospital is affiliated with the prestigious Central South University in Changsha, the capital of central China’s Hunan province. With more than 80 clinical departments, the hospital serves more than 100,000 inpatients and more than 2.1 million outpatients annually.

UPMC announced its first medical services agreement in China in 2011 with the provision of second-opinion pathology consultations to KingMed Diagnostics, the largest independent medical diagnostic laboratory in China. UPMC also has operations or offers services in Italy, Ireland, India, Canada, Singapore, Japan and Kazakhstan. Through its international growth and commercialization efforts with industry partners, UPMC is diversifying its revenue, fueling economic development in its communities, and strengthening its ability to recruit and retain the best and brightest clinicians who are working together to improve health care outcomes globally.

Children’s Physician Receives PCORI Funding for Study on Early Rehabilitation in Pediatric Patients with Acute Brain Injury

PITTSBURGH, August 19, 2014 – Led by a Children’s Hospital of Pittsburgh of UPMC physician, a multidisciplinary research project to improve outcomes for children with acute brain injury was recently approved for a $1.9 million funding award by the Patient-Centered Outcomes Research Institute (PCORI).

The study, “Early Rehabilitation Protocol (ERP) in the Pediatric ICU for Children with Acute Brain Injury (ABI),” led by Ericka Fink, MD, of the Department of Pediatric Critical Care Medicine, will perform a needs assessment to further characterize the current practices, barriers to care, and resources for physical, occupational, speech, and behavioral assessment and therapies needed for ERP implementation in pediatric intensive care units (ICUs). It will also evaluate ERP versus usual care to improve outcomes for children admitted to the ICU with ABI.

The two-center, randomized, controlled trial and resource survey is one of 33 proposals PCORI approved for funding to advance the field of patient-centered comparative effectiveness research and provide patients, health care providers, and other clinical decision makers with information that will help them make better-informed choices.

Dr. Fink and Craig Smith, MD, a former pediatric ICU fellow at Children’s and the principal investigator at Lurie Children’s Hospital, expect that participating sites will perceive an inadequate use of rehabilitation in pediatric ICU patients with ABI and predict that children with ABI will benefit from early ICU rehabilitation rather than usual care.

Pitt Analysis Questions Use of Acute Hemodialysis Treatment

PITTSBURGH, Aug. 20, 2014 – A common approach to treating kidney failure by removing waste products from the blood did not improve survival chances for people who suddenly developed the condition, in an analysis led by experts at the University of Pittsburgh School of Medicine.

Their findings, published online in the journal PLOS One, suggest acute hemodialysis, an aggressive method that is standardly used for people with sudden kidney failure, may not provide a definitive benefit to the patient.

“Our findings question the accepted notion that acute hemodialysis decreases mortality,” said Amber Barnato, M.D., senior author of the study and associate professor of clinical and translational science at the Pitt School of Medicine. Dr. Barnato acknowledges that the study is far from conclusive because it lacks detailed clinical data. “It is impossible to draw conclusions based on an observational study, but I do wonder whether it is time to do a clinical trial on the timing and delivery of acute hemodialysis in the context of acute renal failure and critical illness.”

Dr. Barnato and her team examined records for 2,131,248 patients admitted to Pennsylvania hospitals between October 2005 and December 2007. Some of the patients had varying degrees of kidney failure without end-stage renal disease; 6,657 of those patients had received acute hemodialysis. At one year, patients who received acute hemodialysis had nearly twice the risk of death as similarly ill patients who did not receive acute hemodialysis.

“The most striking finding is the increased mortality risk for patients who received acute hemodialysis, even after risk adjustment which limited the sample to the sickest patients,” said lead author Sarah Ramer, M.D., now of Rutgers New Jersey Medical School, who performed much of the research while a Clinical Scientist Training Program medical student at Pitt. “We know that there is variation in how doctors decide if and when to dialyze a hopspitalized patient. If patients given acute hemodialysis are not carefully chosen, some patients might end up not being helped by the treatment.”

Additional authors on the study are Elan D. Cohen, M.S., and Chung-Chou H. Chang, Ph.D., both of the University of Pittsburgh; and Mark L. Unruh, M.D., now of the University of New Mexico School of Medicine.

Funding for this research was provided by a Doris Duke Clinical Research Fellowship and National Institutes of Health grant R01AG035112.

Magee-Womens Hospital of UPMC Launches First-of-its-Kind Recovery Center for Pregnant Women with Substance Use Challenges

PITTSBURGH, Aug. 20, 2014 – Magee-Womens Hospital of UPMC, in collaboration with four local insurance companies and the Allegheny County Office of Behavioral Health, has launched a comprehensive Pregnancy Recovery Center to provide concurrent treatment for opiate dependence and prenatal care and delivery. The program is one of the first in the country.

The program, created in conjunction with four managed care organizations (Community Care Behavioral Health Organization, UPMC for You, Gateway Health, and United Healthcare for Families and Communities) and Allegheny County, provides pregnant women who struggle with an opiate dependence the opportunity to begin treatment with buprenorphine on an out-patient basis that is integrated with their obstetric services. Like methadone, buprenorphine is a drug used to treat opioid addiction. In addition to the buprenorphine, patients will receive behavioral counseling and clinic visits as well as routine prenatal care. Patients also will meet with social workers and midwives.

“This effort is an excellent example of ways in which payers and providers can come together to develop an innovative initiative that will improve outcomes for pregnant women and their children. We are pleased to have had the opportunity to collaborate with our colleagues,” said John Lovelace, president of UPMC for You.

“For over a decade, Magee has offered drug recovery assistance for pregnant women,” said Dennis H. English, M.D., vice-president of Medical Affairs at Magee. “The key difference between this program and our more traditional methadone program is the Pregnancy Recovery Center operates from the outset on an outpatient basis. The pregnancy recovery center also will provide consistent, collaborative care throughout the patient’s pregnancy.”

According to Dr. English, pregnancy can enhance a woman’s chances at recovering from opiate addiction. The instinct to care for a newborn baby can be a powerful motivating factor for some women.

James Schuster, M.D., M.B.A., chief medical officer of Community Care, notes that, “A key goal of treatment for substance abuse is to help individuals stay engaged in care for at least 90 days. This program is a well-designed effort to support pregnant women in ongoing treatment.”

“Treating pregnant patients with buprenorphine is a relatively new practice,” said Michael Madden, M.D., chief medical officer of Gateway Health. “Early research suggests babies born to mothers taking it instead of undergoing methadone treatment recover more quickly after birth. Recovering from an opiate dependency is a difficult process. We hope this approach will make it easier for our pregnant patients to recover from their dependencies and start their parenting journey confidently and in good health.”

The Pregnancy Recovery Center’s goal is to offer comprehensive care for women suffering from opiate addiction by providing medical support to prevent withdrawal during pregnancy, minimizing fetal exposure to illicit substances and engaging the mother as a leader in her recovery. Women interested in learning more about the program should call 412-641-1211.

Childhood Disability Rates Highest Recorded, Children’s Hospital of Pittsburgh of UPMC Finds

PITTSBURGH, Aug. 18, 2014 – The percentage of children with disabilities due to neurodevelopmental or mental health conditions continues to rise, particularly among children in more socially advantaged households, according to a Children’s Hospital of Pittsburgh of UPMC analysis that appears in the September issue of Pediatrics.

Results of the study, led by Amy Houtrow, M.D., Ph.D., M.P.H., chief, Division of Pediatric Rehabilitation Medicine at Children’s Hospital, found that while there has been a decline in physical health-related disabilities by approximately 12 percent, there was a large, nearly 21 percent rise in disabilities classified as neurodevelopmental or mental health in nature.

The researchers studied data from the National Health Interview Survey conducted by the U.S. Centers for Disease Control and Prevention between 2001 and 2011, evaluating each child’s ability to perform activities at home and school.

Although children living in poverty have the highest rates of disability, children living in families at or above 400 percent of the federal poverty level reported a 28.4 percent increase in disabilities over the past 10-year period.

Dr. Houtrow and the researchers offered four reasons that may explain the increased rates of disability related to neurodevelopmental or mental health conditions:

  • shifts in diagnostic criteria
  • overall increases in rates of certain problems including autism
  • increased awareness of these conditions
  • the need for a specific diagnosis to receive services such as early intervention

“This study demonstrates what a lot of pediatricians have been noticing for several years – that they are seeing more neurodevelopmental and mental health problems in their clinical practices,” said Dr. Houtrow, who also is an associate professor of Physical Medicine & Rehabilitation and Pediatrics and vice chair in the University of Pittsburgh School of Medicine’s Department of Physical Medicine and Rehabilitation. “As we look toward the future, the pediatric health care workforce and system needs to adapt to assure the best possible health and functional outcomes for children with disabilities related to neurodevelopmental and mental health conditions.”

The authors concluded that documenting the changes in childhood disabilities is an important step in developing better prevention and treatment strategies and in determining how to create and deliver services to best meet the needs of all children.

Co-investigators were: Kandyce Larson, Ph.D., and Lynn M. Olson, Ph.D., American Academy of Pediatrics; Paul Newacheck, Dr.P.H., University of California San Francisco; and Neal Halfon M.D., M.P.H., University of California Los Angles.

The research was funded by grants K12H133B031102 and T76MC000141900 from the National Institutes of Health and Department of Health and Human Services.

For more information on Dr. Houtrow and the Division of Pediatric Rehabilitation Medicine, visit http://www.chp.edu/rehab.

Older Adults with Depression and Mild Cognitive Impairment are More Vulnerable to Accelerated Brain Aging, Pitt Study Says

PITTSBURGH, Aug. 7, 2014 – People who develop depression and mild cognitive impairment (MCI) after age 65 are more likely to have biological and brain imaging markers that reflect a greater vulnerability for accelerated brain aging, according to a study conducted by researchers at the University of Pittsburgh School of Medicine. The findings were published online in Molecular Psychiatry.

Older adults with major depression have double the risk of developing dementia in the future compared with those who have never had the mood disorder, said senior investigator Meryl A. Butters, Ph.D., associate professor of psychiatry, Pitt School of Medicine. But there’s no clear explanation for why a treatable mood disorder like depression leads to increased risk for dementia, a progressive brain disease. Until now, most studies have examined only one or two biomarkers to get at this question.

“Our study represents a significant advance because it provides a more comprehensive and integrated view of the neurobiological changes related to mild cognitive impairment in late-life,” she said. “Better understanding of the neurobiology of cognitive impairment in depression can provide new targets for developing more specific treatments, not only for its prevention and treatment, but also for its down-stream negative outcomes, including the development of dementia and related disorders.”

The team collected blood samples from 80 older adults in remission after being treated for major depression, 36 of whom had MCI and 44 with normal cognitive function. Their blood was tested for 242 proteins involved in biologic pathways associated with cancer, cardiovascular diseases, and metabolic disorders as well as psychiatric and neurodegenerative disorders. The researchers also performed PET and MRI brain scans on the participants to look for indicators of cerebrovascular disease, brain atrophy or shrinkage, and beta-amyloid, which is the protein that makes up the brain plaques associated with Alzheimer’s disease.

The MCI group was more likely to have differences in the biologic activity of 24 proteins that are involved in the regulation of immune and inflammatory pathways, intracellular signaling, cell survival, and protein and lipid balance.

Brain scans revealed a greater propensity for cerebrovascular disease – for example, small strokes – in the MCI group, but there was no difference in the amount of beta-amyloid deposition.

“If you take these results altogether, they suggest that people with depression and cognitive impairment may be more vulnerable to accelerated brain aging, which in turn puts them at risk for developing dementia,” Dr. Butters said. “Ultimately, if we can understand what happens in the brain when people are depressed and suffer cognitive impairment, we can then develop strategies to slow or perhaps stop the impairment from progressing to dementia.”

Next steps include assessing the protein panel in older people with normal cognitive function who have not experienced depression.

Co-authors of the study include Etienne Sibille, Ph.D., Ying Ding, Ph.D., George Tseng, Ph.D., Howard Aizenstein, M.D., Ph.D., Frances Lotrich, M.D., Ph.D., James T. Becker, Ph.D., Oscar L. Lopez, M.D., Michael T. Lotze, M.D., William E. Klunk, M.D., Ph.D., and Charles F. Reynolds, M.D., all of the University of Pittsburgh; and the first author is Breno S. Diniz, M.D., Ph.D., now of the Federal University of Minas Gerais, Brazil.

The project was funded by National Institutes of Health grants MH080240, MH90333 (ACISR for Late Life Depression Prevention and Treatment), AG05133 (Alzheimer Disease Research Center), MH09456; CA047904-22S1, CA160417, CA181450; the John A. Hartford Foundation Center of Excellence in Geriatric Psychiatry; and the Brazilian Intramural Research Program.

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